The cause and effect relationship between ectopic endometrial cell growth and characteristic local inflammatory response is unknown but is probably of fundamental importance in endometriosis (E). We are proposing to investigate this relationship and have formed two interrelated hypotheses to be tested. According to the first one, the distinct macrophage response in the peritoneal cavity in patients with E may be responsible for enhanced survival of endometrial cells. The second hypothesis assumes that an intrinsic biologic difference may exist in either all or only in ectopic cells of endometrial origin in patients with E as compared to those of normal women (N). This "abnormality" may increase their survival in the peritoneal environment and directly lead to a distinct macrophage response. Our recent studies have identified differnces in macrophage membrane function and in vitro differentiation in N and E patients. In order to study the biologic relevance of these phenomena we will determine if macrophages from N and E secrete factors stimulating endometrial cell growth and whether this can be influenced by the stage of macrophage maturation or by sex steroids/danazol. Biologic characterization of endometrial cells will be attempted since these cells in E may have a basic alteration in growth regulation and this may be reflected either by the response to exogenous growth factors or by altered expression of the normal growth regulatory cellular oncogenes. In order to test this hypothesis, proliferative response of endometrial cells of N and E patients to several known growth stimulating factors will be tested and tissue specimens will be analyzed for enhanced or suppressed expression of critical oncogenes. If enhanced expression of an oncogene is found in either ectopic or eutopic cells in E, gene amplification and the possibility of genomic alterations will be assessed. Due to the lack of availability of large amounts of human cells and variability of individual specimens it is imperative that we produce long-term cell lines. We will attempt to establish immortalized macrophage and endometrial cell lines from N and E patients by viral transfection. These would provide a unique resource for detailed characterization of the various factors, cellular growth requirements and interactions between the two cell types. They would ultimately permit a direct assessment of the role of altered oncogene expression.